Local delivery of therapeutic agents to target organs or tissues is a very desirable technique for delivering drugs with minimal side effects. U.S. Pat. No. 5,087,244 is an example of such targeted drug delivery, in which an endovascular catheter has a flexible balloon that is inflated to contact the internal walls of the vessel. A drug is then delivered through minute holes in the balloon, which is in intimate contact with the walls of the vessel. U.S. Pat. No. 5,282,785 discloses another endovascular drug delivery catheter, in which an expandable balloon brings a perforated drug delivery portion of the catheter into intimate contact with a radially restricted portion of the vessel wall, for transmural delivery of drugs through the contiguous catheter and lumen wall. See also U.S. Pat. No. 5,662,609, according to which a catheter with a pair of expandable balloons is used to isolate a portion of a blood vessel between the balloons for treatment via infusions, and U.S. Pat. No. 5,674,192, in which a single expandable balloon is used to contact a portion of vessel wall for treatment.
U.S. Pat. Nos. 4,781,677 and 5,514,088 both disclose treatment of gallstones by direct infusion of a solvent (such as methyl tertiary butyl ether) into the gallbladder through a catheter positioned in that organ.
U.S. Pat. No. 5,720,720 discloses high flow microinfusion of drugs (such as chemotherapeutic agents) into the brain parenchyma. Using this approach, a catheter is inserted into a brain tumor, and a chemotherapeutic agent is introduced through the catheter at a sufficient flow rate to cause rapid diffusion of the substance throughout the relatively homogenous, porous medium of the brain.
None of these methods or devices, however, discloses selective delivery of therapeutic substances (such as drugs and DNA vectors) to specific microanatomic regions or cell types in an organ. This is a significant drawback because many diseases involve abnormalities that are restricted to particular microanatomic or cellular regions. General systemic delivery of a therapeutic substance at a sufficient concentration to reach this localized region can cause widespread toxicity. General systemic delivery of drugs and gene therapy vectors can also be much less effective than site directed delivery, because selected delivery introduces the drug or vector directly into the tissue where it is to act. Site specific delivery can be accomplished to a certain degree by use of tissue-specific ligands, but the availability of identified ligands, and the degree of specificity of known ligands, may be insufficient to prevent negative systemic effects. The discovery and design of such ligands is also a complex, time-consuming and expensive process.
It is thus an object of the present invention to provide improved regional and tissue- or cell-specific delivery of therapeutic (including diagnostic) agents.